The invention relates generally to bicyclic carbohydrates and, more specifically to furanose-type bicyclic carbohydrates that have antiviral and cytostatic activity.
Cytomegalovirus, or CMV, is found universally throughout all geographic locations and socio-economic groups, and infects between 50% and 85% of adults in the United States by 40 years of age. CMV is also the virus most frequently transmitted to a developing child before birth. CMV infection is more widespread in developing countries and in areas of lower socio-economic conditions. For most healthy persons who acquire CMV after birth there are few symptoms and no long-term health consequences. Some persons with symptoms experience a mononucleosis-like syndrome with prolonged fever, and a mild hepatitis. Once a person becomes infected, the virus remains alive, but usually dormant within that person's body for life. Recurrent disease rarely occurs unless the person's immune system is suppressed due to therapeutic drugs or disease. Therefore, for the vast majority of people, CMV infection is not a serious problem.
However, CMV infection is important to certain high-risk groups. Major areas of concern are (1) the risk of infection to the unborn baby during pregnancy, (2) the risk of infection to people who work with children, and (3) the risk of infection to the immuno-compromised person, such as organ transplant recipients and persons infected with human immunodeficiency virus (HIV).
CMV is a member of the herpesvirus group, which includes herpes simplex virus types 1 and 2, varicella-zoster virus (which causes chickenpox), and Epstein-Barr virus (which causes infectious mononucleosis). Infectious CMV may be shed in the bodily fluids of any previously infected person, and thus may be found in urine, saliva, blood, tears, semen, and breast milk. The shedding of virus may take place intermittently, without any detectable signs, and without causing symptoms.
Most infections with CMV are not diagnosed because the virus usually produces few, if any, symptoms and tends to reactivate intermittently without symptoms. However, persons who have been infected with CMV develop antibodies to the virus, and these antibodies persist in the body for the lifetime of that individual. A number of laboratory tests that detect these antibodies to CMV have been developed to determine if infection has occurred and are widely available from commercial laboratories. In addition, the virus can be cultured from specimens obtained from urine, throat swabs, and tissue samples to detect active infection.
Currently, no treatment exists for CMV infection in the healthy individual. Antiviral drug therapy is now being evaluated in infants. Ganciclovir (DHPG) treatment is used for patients with depressed immunity that have either sight-related or life-threatening illnesses. Other products that are used to treat CMV infections are the nucleoside analogue (S)—HPMPC (Cidofovir) and the phosphonate analogue Foscarnet (Foscavir). However, all these treatments have drawbacks such as toxicity problems and the building up of resistance. Vaccines are still in the research and development stage.
Recently, researchers all over the world are getting more and more aware that sugars play an extremely important role in living creatures. It turns out that sugars are involved in almost every aspect in biology, from recognizing pathogens, to blood clotting, to enabling sperm to penetrate an ovum. Biologists are only just beginning to come to grips with these important sugars, but as they do they are finding themselves having to rethink long-held ideas about how life works (K. Schmidt; Sugar rush. New Scientist, (26 Oct. 2002) 34-38). This importance of sugars is demonstrated by the fact that in addition to the terms “genomics” and “proteomics”, the term “glycomics” is now being used.
This underlines the importance of product groups containing sugars, to which also the bicyclic carbohydrate derivatives described in this specification belong. In other work, the synthesis and properties of a series of bicyclic carbohydrates based on pyranose sugars has been described.